Daklinza (trade name of Daclatasvir dihydrochloride) Daclatasvir is a drug for the treatment of hepatitis C (HCV), genotype 3 infections. Daclatasvir inhibits the HCV nonstructural protein NS5A. Recent research suggests that it targets two steps of the viral replication process, enabling rapid decline of HCV RNA. Daclatasvir dihydrochloride is chemically known as methyl((1S)-1-(((2S)-2-(5-(4′-(2-((2S)-1-((2S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-2-pyrrolidinyl)-1H-imidazol-5-yl)-4-biphenylyl)-1H-imidazol-2-yl)-1-pyrrolidinyl)carbonyl)-2-methylpropyl) carbamate dihydrochloride has the following structure.

Daclatasvir dihydrochloride was first described in Example 24-23 of U.S. Pat. No. 8,329,159 B2, wherein the process is disclosed by reacting 1,1′-biphenyl-4,4′-diylbis(2-bromoethanone) with compound of formula (IV) in presence of base to produce compound of formula (V), further it was cyclized in presence of NH4OAc and followed by deprotection in presence of acidic conditions to obtained compound of formula (VII). This on reacted with compound of formula (VIII) in presence of HOBt hydrate, DIPEA, EDC1.HCl and hydrochloric acid to get Daclatasvir dihydrochloride (I).
The above said process is schematically shown as below:

According to the above prior art processes which involves the condensation reaction of compound of formula (III) with 1-(tert-butoxycarbonyl)-L-proline in presence of base causes low yield and high impurity profile.
Hence, the use of base may not feasible and it is not economical for industrial scale for the preparation of Daclatasvir dihydrochloride (I).
WO 2016178250 discloses a process for the preparation of Daclatasvir dihydrochloride which is comprises compound of formula (IX) undergoes acetylation to get a compound of formula (X), this on followed by reacted with compound of formula (XI) to obtain a compound of formula (XII). The product of step ii is reacted with compound of formula (IVa) and followed by reacted with compound of formula (XI) to give a compound of formula (XIV), later reacted with compound of formula (IVa) to get a compound of formula (Va) further it converts into compound of formula (VIa), followed by deprotection and reacted with compound of formula (VIII) to obtain Daclatasvir dihydrochloride, which is depicted in the scheme-II given below:

The process of WO '250 discloses various disadvantages in the reaction management which has particularly more reactive steps for preparation of the Daclatasvir dihydrochloride on the industrial scale.
CN 105461701 A discloses process for the preparation of Daclatasvir dihydrochloride, which comprises the compound of formula (III) is reacted with compound of formula (XV) and followed by cyclisation in presence of ammonium acetate to get Daclatasvir dihydrochloride (I).

In view of the foregoing, the present inventors have result of extensive studies, the efficiency is extremely only the condensation reaction of compound of formula (III) with potassium 1-(tert-butoxycarbonyl)-L-proline is carried out in absence of base, it was found that the corresponding (2R,2′R)—O′2,O2-([1,1′-biphenyl]-4,4′-diylbis(2-oxoethane-2,1-diyl))1-di-tert-butyl bis(pyrrolidine-1,2-dicarboxylate) can be produced in high yield and purity with advantages of low consumption of solvents.
The present inventors are also concluded that coupling reaction of PTSA salt of compound of formula (VIIc) with methoxy carbonyl L-valine of formula (VIII) is carried out in presence of coupling agent to affords Daclatasvir dihydrochloride with high purity, less impurity and good yield.